Cancer risk with Simvastatin and Ezetimibe (Vytorin)?
admin August 22nd, 2008
The FDA have issued an Early Communication about an Ongoing Safety Review concerning a potentially increased risk of cancer associated with Simvastatin and Ezetimibe when used in combination (Vytorin).
FDA informed healthcare professionals that the Agency is investigating a report from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of a possible association between the use of Vytorin and a potentially increased incidence of cancer. Vytorin is a combination product of simvastatin and ezetimibe used to decrease the production of cholesterol by the liver and inhibit the absorption of cholesterol in the intestine to reduce LDL-cholesterol levels and reduce the risk of cardiovascular events. Recently, FDA obtained preliminary results from the SEAS trial. The clinical trial tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of cardiovascular events in individuals with aortic stenosis. A lower overall cardiovascular risk was not found with Vytorin. However, there was an additional observation that a larger percentage of subjects treated with Vytorin were diagnosed with and died from all types of cancer combined when compared to placebo during the 5-year study.
FDA anticipates receiving a final SEAS study report in about 3 months and the Agency’s review and evaluation of the clinical trial data and other relevant information should take approximately 6 months. FDA will communicate its conclusions and recommendations at that time. Healthcare professionals and caregivers should continue to monitor patients taking Vytorin and report side effects from the use of this drug to the Agency.
The risk reported in the SEAS trial is noted here:
An adverse event attributable to cancer was noted more frequently in the ezetimibe/simvastatin arm, as compared with placebo (9.9% vs. 7.0%, p = 0.03). Cancer deaths were also more frequent in the ezetimibe/simvastatin arm (4.1% vs. 2.5%, p = 0.05). On further scrutiny, these differences did not seem to be related to any particular type of cancer and did not become significantly larger with more prolonged treatment.
There is already controversy about this news in the media, with the democratic chairman of the U.S. House of Representatives Energy and Commerce Committee getting confused by an apparent discrepancy in cancer figures. This is a red herring related to two snapshots of the trial data release from two differing sources. It should not be taken as evidence of harms being hidden, although it is a shame that calm rational discussion of the possible risk may be derailed by confusion about figures.
As the FDA notes there are two large ongoing trials (IMPROVE-IT and SHARP) being undertaken of the simvastatin/ezetimibe combination, and the full results of the SEAS study are not yet available. Interim data from IMPROVE-IT and SHARP do not show this result. Therefore some caution is required in interpretation of these preliminary results from SEAS.
The FDA are therefore not advising patients to stop or switch treatment, and nor are they suggesting there is a causal relationship between the combination and cancer. They expect to finish their review in 6 months time.
In years gones by regulators may have avoided statements related to associations that where not proven. Improvements in transparency and communications mean that regulators are attempting to be open about their decision making processes. That means sharing information about potential adverse effects – even when proof does not exist. Hopefully, the media and public will accept this for what it is, rather than being alarmed by the information provided.